Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19761 | 59506;59507;59508 | chr2:178592838;178592837;178592836 | chr2:179457565;179457564;179457563 |
| N2AB | 18120 | 54583;54584;54585 | chr2:178592838;178592837;178592836 | chr2:179457565;179457564;179457563 |
| N2A | 17193 | 51802;51803;51804 | chr2:178592838;178592837;178592836 | chr2:179457565;179457564;179457563 |
| N2B | 10696 | 32311;32312;32313 | chr2:178592838;178592837;178592836 | chr2:179457565;179457564;179457563 |
| Novex-1 | 10821 | 32686;32687;32688 | chr2:178592838;178592837;178592836 | chr2:179457565;179457564;179457563 |
| Novex-2 | 10888 | 32887;32888;32889 | chr2:178592838;178592837;178592836 | chr2:179457565;179457564;179457563 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/S | rs563969986  |
-1.102 | 0.999 | N | 0.612 | 0.561 | None | gnomAD-2.1.1 | 3.85852E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.50525E-03 | None | 0 | None | 0 | 0 | 1.40449E-04 |
| N/S | rs563969986 |
-1.102 | 0.999 | N | 0.612 | 0.561 | None | gnomAD-3.1.2 | 2.56366E-04 | None | None | None | None | N | None | 0 | 5.24246E-04 | 0 | 0 | 5.62452E-03 | None | 0 | 0 | 0 | 0 | 9.56023E-04 |
| N/S | rs563969986 |
-1.102 | 0.999 | N | 0.612 | 0.561 | None | 1000 genomes | 7.98722E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 4E-03 | 0 | None | None | None | 0 | None |
| N/S | rs563969986 |
-1.102 | 0.999 | N | 0.612 | 0.561 | None | gnomAD-4.0.0 | 3.04919E-04 | None | None | None | None | N | None | 0 | 1.33373E-04 | None | 0 | 1.0226E-02 | None | 0 | 0 | 4.23868E-06 | 1.09803E-05 | 3.20174E-04 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.9851 | likely_pathogenic | 0.9814 | pathogenic | -0.799 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| N/C | 0.8983 | likely_pathogenic | 0.9031 | pathogenic | -0.652 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| N/D | 0.9792 | likely_pathogenic | 0.9717 | pathogenic | -2.185 | Highly Destabilizing | 0.999 | D | 0.623 | neutral | N | 0.521561082 | None | None | N |
| N/E | 0.9968 | likely_pathogenic | 0.9956 | pathogenic | -2.025 | Highly Destabilizing | 0.999 | D | 0.727 | prob.delet. | None | None | None | None | N |
| N/F | 0.9987 | likely_pathogenic | 0.9982 | pathogenic | -0.71 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| N/G | 0.9737 | likely_pathogenic | 0.9672 | pathogenic | -1.108 | Destabilizing | 0.999 | D | 0.591 | neutral | None | None | None | None | N |
| N/H | 0.9664 | likely_pathogenic | 0.9562 | pathogenic | -0.754 | Destabilizing | 1.0 | D | 0.772 | deleterious | D | 0.534095929 | None | None | N |
| N/I | 0.9879 | likely_pathogenic | 0.9862 | pathogenic | -0.01 | Destabilizing | 1.0 | D | 0.765 | deleterious | D | 0.552707163 | None | None | N |
| N/K | 0.9977 | likely_pathogenic | 0.9967 | pathogenic | -0.27 | Destabilizing | 1.0 | D | 0.751 | deleterious | D | 0.533335461 | None | None | N |
| N/L | 0.964 | likely_pathogenic | 0.9578 | pathogenic | -0.01 | Destabilizing | 1.0 | D | 0.765 | deleterious | None | None | None | None | N |
| N/M | 0.9851 | likely_pathogenic | 0.9824 | pathogenic | 0.236 | Stabilizing | 1.0 | D | 0.792 | deleterious | None | None | None | None | N |
| N/P | 0.9963 | likely_pathogenic | 0.9943 | pathogenic | -0.246 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| N/Q | 0.9971 | likely_pathogenic | 0.9959 | pathogenic | -1.226 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | N |
| N/R | 0.996 | likely_pathogenic | 0.994 | pathogenic | -0.178 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| N/S | 0.6053 | likely_pathogenic | 0.6033 | pathogenic | -1.126 | Destabilizing | 0.999 | D | 0.612 | neutral | N | 0.500099011 | None | None | N |
| N/T | 0.8121 | likely_pathogenic | 0.8268 | pathogenic | -0.81 | Destabilizing | 0.999 | D | 0.717 | prob.delet. | N | 0.472507647 | None | None | N |
| N/V | 0.9787 | likely_pathogenic | 0.9752 | pathogenic | -0.246 | Destabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | N |
| N/W | 0.9996 | likely_pathogenic | 0.9993 | pathogenic | -0.643 | Destabilizing | 1.0 | D | 0.771 | deleterious | None | None | None | None | N |
| N/Y | 0.9925 | likely_pathogenic | 0.9886 | pathogenic | -0.243 | Destabilizing | 1.0 | D | 0.779 | deleterious | D | 0.552453674 | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.